The Peptide Synthesis Facility (PSF) provides cost-effective syntheses of highly purified synthetic peptide sequences to M. D. Anderson investigators. Since our last submission in 1997, the PSF has increased the number of peptides provided to M. D. Anderson investigators, 228 in 2001 vs 123 in 1997, and has increased the percentage of peptides provided to peer-reviewed users has increased 85% since 1997. Although the number of users utilizing the services of the PSF has not increased, 27 in both 2001 and 1997, the types of peptides being requested as well as the personnel requesting them have shifted dramatically. The users come from 20 programs. The vast majority of peptide requests received by the PSF have changed from requests for B-cell epitopes for the purpose of generating site-specific antibodies to requests for MHC Class I and Class II T-cell epitopes. The cytotoxic T-lymphocyte (CTL) specific sequences are extremely hydrophobic and necessitated changes in our methods of peptide purification. Additionally, with the advent of new reagents, we have become proficient at providing purified phosphopeptides to investigators for generating phosphopeptide-specific antibodies. Since 1999, the institution has provided 3 new state-of-the-art peptide synthesizers and 1 new analytic high performance liquid chromatography (HPLC) system to the PSF. With these new instruments, we have changed the chemistry of producing synthetic peptides and have changed the programs used to generate peptides. Our new programs operate at much higher efficiency, enabling equivalent amounts of purified peptides to be generated with substantial savings in reagents. These savings have enabled the PSF to provide M. D. Anderson investigators with cost effective peptides without invoking annual price increases. The current funding for the PSF is CCSG (30%), user fees (20%), and institutional sources (50%). Among the scientific achievements supported by the facility are a number of vaccines, enzyme inhibitors, and phospho-peptide specific antibodies. Peptides we provided to an M. D. Anderson investigator were used in a peptide cocktail vaccine to prevent chronic HIV infection. The peptides prepared in the PSF with di-lipid tails were injected into rhesus monkeys with autologous dendritic cells. The vaccinated animals exhibited CTL induction and T-cell proliferation but no B-cell (antibody) responses. Upon challenge with the pathogenic SHIV virus, the vaccinated animals were able to efficiently clear the virus to undetectable levels within 14 weeks. Another investigator consulted with the PSF to find a way to enhance the specific CTL receptor binding to a known breast cancer epitope. PSF personnel altered specific amino acids within that epitope by adding or subtracting a single methylene group while maintaining amino structure. The result was enhanced CTL activity, maintenance of CTL specificity, and a patent application for M. D. Anderson. In the future we plan to improve the efficiency of our service to provide faster throughput.